The use of saphenous veins in aortocoronary bypass grafts has become a common surgical treatment for various forms of ischemic heart disease. Even though the functional longevity of saphenous vein bypass grafts is increasing, graft failure due to thrombosis, wall hypertrophy and spontaneous vasospasm, is still a problem. The ultimate objective of this grant is to arrive at improved handling procedures that result in improved graft performance, that is, increased graft longevity. The experimental design to obtain this object is to: 1) identify biochemical and pharmacological changes that occur in the saphenous vein following grafting and to relate these to observed contractile and mechanical characteristics; 2) identify the stimuli responsible for these changes which in turn, would suggest possible modifications in graft handling techniques that would minimize these changes; and 3) identify the cellular alteration responsible for the functional changes. To these various ends, the work performed to date has identified three alterations in the saphenous vein graft: 1) hypertrohy of the vessel wall; 2) increased sensitivity to the physiological vasoconstrictor norepinepherine; and 3) decreased maximum contractile performance. The last two changes have not previously been identified as occurring with grafting and may contribute to spontaneous vasospasm. The work also suggests that the hypertorphy and increased catechloaminesensitivity are due in part to an increase in transmural pressure and denervation, respectively. The reduction in actomyosin force generating capacity may result from qualitative changes in actin and/or myosin, structural reorganization of the vessel wall, or availability of calcium for contractile activation. Based on these observations, several questions are raised which form the basis for the work described in this application: 1) Do these changes continue to progress to vessel occlusion, to a new steady state different than control, or do they return to control values? 2) What are the roles of oxygen, transmural pressure, and endothelial damage in initiating these changes and can handling procedures be altered to reduce the effect of these possible stimuli? 3) What are the cellular changes responsible for the increase in catecholamine sensitivity and the reduction in actomyosin force generating capacity?